tbuckley/cabot-search huggingface dataset:
A global core outcome measurement set for snakebite clinical trials
Authors: Michael Abouyannis, Hanif Esmail, Mainga Hamaluba, Mwanajuma Ngama, Hope Mwangudzah, Noni Mumba, Betty K Yeri, Salim Mwalukore, Hassan J Alphan, Dinesh Aggarwal, Gabriel Alcoba, Nick Cammack, Jean-Philippe Chippaux, Matthew E Coldiron, José M Gutiérrez, Abdulrazaq G Habib, Robert A Harrison, Geoffrey K Isbister, Eric J Lavonas, Diogo Martins, Isabela Ribeiro, James A Watson, David J Williams, Nicholas R Casewell, Sarah A Walker, David G Lalloo, Michael Abouyannis, Dinesh Aggarwal, Gabriel Alcoba, Hassan J Alphan, Nick Cammack, Nicholas R Casewell, Jean-Philippe Chippaux, Matthew E Coldiron, Hanif Esmail, José M Gutiérrez, Abdulrazaq G Habib, Mainga Hamaluba, Robert A Harrison, Geoffrey K Isbister, David G Lalloo, Eric J Lavonas, Diogo Martins, Noni Mumba, Salim Mwalukore, Hope Mwangudzah, Mwanajuma Ngama, Isabela Ribeiro, A Sarah Walker, James A Watson, David J Williams, Betty K Yeri, Chanaveerappa Bammigatti, Rebecca W Carter, Charles J Gerardo, H Janaka de Silva, Thomas Lamb, Matthew R Lewin, Wuelton Monteiro, Ymkje Stienstra
Journal: The Lancet Global Health (2023)

Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Five universal core outcome measures should be included in all future snakebite clinical trials—mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.
Mutational analysis of microsatellite-stable gastrointestinal cancer with high tumour mutational burden: a retrospective cohort study
Authors: Jingyuan Wang, Joanne Xiu, Alex Farrell, Yasmine Baca, Hiroyuki Arai, Francesca Battaglin, Natsuko Kawanishi, Shivani Soni, Wu Zhang, Joshua Millstein, Anthony F Shields, Axel Grothey, Benjamin A Weinberg, John L Marshall, Emil Lou, Moh'd Khushman, Davendra P S Sohal, Michael J Hall, Tianshu Liu, Matthew Oberley, David Spetzler, W Michael Korn, Lin Shen, Heinz-Josef Lenz
Journal: The Lancet Oncology (2023)
Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood: a prospective cohort study
Authors: Mohamed Ghalwash, Vibha Anand, Olivia Lou, Frank Martin, Marian Rewers, Anette-G Ziegler, Jorma Toppari, William A Hagopian, Riitta Veijola, Peter Achenbach, Ezio Bonifacio, Claire Crouch, Jessica Dunne, Helena Elding Larsson, Brigitte I Frohnert, Jianying Hu, Heikki Hyöty, Jorma Ilonen, Josefin Jönsson, Michael Killian, Mikael Knip, Eileen Koski, Åke Lernmark, Ying Li, Zhiguo Li, Bin Liu, Markus Lundgren, Ashwani Malhotra, Marlena Maziarz, Jocelyn Meyer, Shelley Moore, Kenney Ng, Jill Norris, Shreya Roy, Lampros Spiliopoulos, Andrea Steck, Harry Stavropoulos, Kathleen Waugh, Christiane Winkler, Liping Yu
Journal: The Lancet Child & Adolescent Health (2023)
Preprints versus peer-reviewed articles
Authors: Kent R Anderson
Journal: The Lancet Global Health (2023)

I have some concerns over the Health Policy paper by Lindsay Nelson and colleagues (November, 2022)1Nelson L Ye H Schwenn A Lee S Arabi S Hutchins BI Robustness of evidence reported in preprints during peer review.Lancet Glob Health. 2022; 10: e1684-e1687Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar on the robustness of evidence reported in preprints during peer review. There are data discrepancies between the dataset used and what was reported, and although the authors claimed to compare data within unreviewed preprints with data from peer-reviewed manuscripts, nearly 20% of the papers analysed consisted of preprints posted after the paper had been accepted by the publishing journal. The data discrepancies include only 96 preprint–paper pairs being included, not the 100 reported in the manuscript; and the data source (the NIH iSearch COVID-19 Portfolio) not accounting for multiple versions of preprints (33 of 96 preprints have more than one version), not always linking to the initial version, and not reconciling duplicate postings across preprint servers (three instances). More importantly, comparing the date of the initial preprint posting with various publication-related events (submission date, acceptance date, and publication date), 19 (19·8%) of 96 articles had preprints that were posted after journal acceptance. In addition, five (5·2%) of 96 articles were posted as preprints on or after the publication date of the peer-reviewed article. Conceptually, the paper has a fundamental problem, in that it is unknown (and unknowable) how much peer-review might have occurred before any documented submission event, as only submission events that lead to publication events are recorded publicly. Specifically, the paper lacks the proper controls to state with confidence that it tested non-reviewed preprints with peer-reviewed manuscripts, as nearly a fifth of published articles have documented evidence that peer review and editorial acceptance occurred prior to the comparator preprint being posted. I declare no competing interests. Robustness of evidence reported in preprints during peer reviewScientists have expressed concern that the risk of flawed decision making is increased through the use of preprint data that might change after undergoing peer review. This Health Policy paper assesses how COVID-19 evidence presented in preprints changes after review. We quantified attrition dynamics of more than 1000 epidemiological estimates first reported in 100 preprints matched to their subsequent peer-reviewed journal publication. Point estimate values changed an average of 6% during review; the correlation between estimate values before and after review was high (0·99) and there was no systematic trend. Full-Text PDF Open Access
A practical approach to curate clonal hematopoiesis of indeterminate potential in human genetic datasets
Authors: Caitlyn Vlasschaert, Taralynn Mack, Jonathan Brett Heimlich, Abhishek Niroula, Md Mesbah Uddin, Joshua S Weinstock, Brian Sharber, Alexander J. Silver, Yaomin Xu, Michael R. Savona, Christopher J. Gibson, Matthew B. Lanktree, Michael J Rauh, Benjamin L. Ebert, Pradeep Natarajan, Siddhartha Jaiswal, Alexander G. Bick
Journal: Blood (2023)
Multishell Colloidosome Platform with Sequential Gastrointestinal Resistance for On‐Demand Probiotic Delivery
Authors: Xin Xie, Qinyuan Li, Lufan Jia, Hao Yuan, Ting Guo, Tao Meng
Journal: Advanced Healthcare Materials (2023)

Abstract Probiotic‐based oral therapy can potentially prevent and treat diseases by regulating the balance of intestinal flora. However, significant loss of viability and bioactivity of probiotics before reaching the colon results in low delivery efficiency and therapeutic effects, which limits their clinical applications. Here, this work proposes a multishell colloidosome (MSC) platform with sequential gastrointestinal resistance for on‐demand probiotic delivery based on biomimetic mineralization and microfluidic technology. Notably, the viability of the decorated probiotics increases 280‐fold compared to that of free bacteria during preservation. Because of the sequential gastrointestinal resistance of MSC, encapsulated probiotics exhibit high viability (61%) under continuous exposure to extreme acidity, bile salt erosion, and enzymatic action, whereas free bacteria have a viability of 0%. Moreover, in vitro and in vivo studies reveal that MSC mainly releases probiotics in the colon and improves colonic colonization by probiotics to maintain the integrity of the intestinal barrier and regulate the balance of intestinal flora. Consequently, MSC significantly improves the therapeutic effect on colitis in mice. The MSC platform provides a promising delivery strategy to enhance the efficacy of orally administered probiotics.
Multi-omics profiling of cholangiocytes reveals sex-specific chromatin state dynamics during hepatic cystogenesis in polycystic liver disease
Authors: Rongjie Ji, Jiayuan Chen, Yuyang Xie, Xudan Dou, Bo Qing, Zhiheng Liu, Yumei Lu, Lin Dang, Xu Zhu, Ying Sun, Xiangjian Zheng, Lirong Zhang, Dong Guo, Yupeng Chen
Journal: Journal of Hepatology (2023)
Letters to Clinicians May Promote Better-Informed Opioid Prescribing
Authors: Howard D. Larkin
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
AAP Recommends Immediate, Intensive Treatment for Child Obesity
Authors: Howard D. Larkin
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Gut microbiota promote liver regeneration through hepatic membrane phospholipid biosynthesis
Authors: Yuhan Yin, Anna Sichler, Josef Ecker, Melanie Laschinger, Gerhard Liebisch, Marcus Höring, Marijana Basic, André Bleich, Xue-Jun Zhang, Ludwig Kübelsbeck, Johannes Plagge, Emely Scherer, Dirk Wohlleber, Jianye Wang, Yang Wang, Marcella Steffani, Pavel Stupakov, Yasmin Gärtner, Fabian Lohöfer, Carolin Mogler, Helmut Friess, Daniel Hartmann, Bernhard Holzmann, Norbert Hüser, Klaus-Peter Janssen
Journal: Journal of Hepatology (2023)
Mitochondrial pyruvate carrier 1 regulates fatty acid synthase lactylation and mediates treatment of nonalcoholic fatty liver disease
Authors: Ruxin Gao, Yue Li, Zhimeng Xu, Feng Zhang, Jia Xu, Yanzhou Hu, Jingya Yin, Kun Yang, Lei Sun, Qi Wang, Xiaoyun He, Kunlun Huang
Journal: Hepatology (2023)

Background and Aims: NAFLD has become a major metabolic disease worldwide. A few studies have reported the potential relationship between mitochondrial pyruvate carrier 1 (MPC1) and inflammation, fibrosis, and insulin sensitivity in obese or NASH mouse models. However, the impact of MPC1 on NAFLD-related liver lipid metabolism and its role in the NAFLD progression require further investigation. Approach and Results: MPC1 expression was measured in liver tissues from normal controls and patients with NAFLD. We characterized the metabolic phenotypes and expression of genes involved in hepatic lipid accumulation in MPC1 systemic heterozygous knockout (MPC1 +/− ) mice. Hepatic protein lactylation was detected using Tandem Mass Tags proteomics and verified by the overexpression of lactylation mutants in cells. Finally, the effect of MPC1 inhibition on liver inflammation was examined in mice and AML-12 cells. Here, we found that MPC1 expression was positively correlated to liver lipid deposition in patients with NAFLD. MPC1 +/− mice fed with high-fat diet had reduced hepatic lipid accumulation but no change in the expression of lipid synthesis-related genes. MPC1 knockout affected the lactylation of several proteins, especially fatty acid synthase, through the regulation of lactate levels in hepatocytes. Lactylation at the K673 site of fatty acid synthase inhibited fatty acid synthase activity, which mediated the downregulation of liver lipid accumulation by MPC1. Moreover, although MPC1 knockout caused lactate accumulation, inflammation level was controlled because of mitochondrial protection and macrophage polarization. Conclusions: In NAFLD, MPC1 levels are positively correlated with hepatic lipid deposition; the enhanced lactylation at fatty acid synthase K673 site may be a downstream mechanism.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2023)

Immune Synergy Is Required for Cancer VaccinationCancer vaccines promise a broad and affordable alternative to protein and cell-based cancer immunotherapies.Utilizing SNP-7/8a, a selfassembling nanoparticle vaccine that combined expression of an engineered cancer neoantigen with a Toll-like receptor 7/8 agonist, Baharom and colleagues revealed separable importance for both CD8 þ T cells and innate signaling in mediating therapeutic efficacy.Subcutaneous delivery of SNP-7/8a was sufficient to elicit a CD8 þ T-cell response equivalent to intravenous SNP-7/8a.However, only intravenous delivery led to accumulation of SNP in tumors, leading to a systemic increase in inflammatory cytokines, most importantly, IFNa.Antibody blockade of IFNa signaling reversed the efficacy of intravenous SNP, as IFNa was necessary for the reduction of a subset of immunosuppressive (Chil3 þ ) monocytes within tumors.Patients with renal cell or glial tumors expressing high levels of Chil3 exhibited worse prognoses.
Bivalent Omicron BA.1–Adapted BNT162b2 Booster in Adults Older than 55 Years
Authors: Patricia Winokur, Juleen Gayed, David Fitz-Patrick, Stephen J Thomas, Oyeniyi Diya, Stephen Lockhart, Xia Xu, Ying Zhang, Vishva Bangad, Howard I Schwartz, Douglas Denham, Jose F Cardona, Lisa Usdan, John Ginis, Federico J Mensa, Jing Zou, Xuping Xie, Pei-Yong Shi, Claire Lu, Sandra Buitrago, Ingrid L Scully, David Cooper, Kenneth Koury, Kathrin U Jansen, Özlem Türeci, Uğur Şahin, Kena A Swanson, William C Gruber, Nicholas Kitchin
Journal: New England Journal of Medicine (2023)

The emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019.
Neuroblastoma Differentiation: The Untapped Potential of Mitochondrial Uncouplers
Authors: F.L. Byrne, J.L. Bell
Journal: Cancer Research (2023)

Abstract While the goal of most anticancer treatments is to kill cancer cells, some therapies halt cancer progression by inducing cancer cell differentiation. For example, retinoic acid induces neuroblastoma cell differentiation in vitro and is used as maintenance therapy for children with high-risk neuroblastoma. A new study by Jiang and colleagues has revealed the mitochondrial uncoupler niclosamide ethanolamine (NEN) induces neuroblastoma cell differentiation in vitro and slows neuroblastoma tumor growth in vivo. Mitochondrial uncoupler molecules alter cell metabolism by forcing cells to “burn” more nutrients, resulting in a switch from anabolic to catabolic metabolism. NEN-induced neuroblastoma cell differentiation was associated with disruption of Warburg metabolism, epigenetic remodeling, and downregulation of key oncogenic drivers of neuroblastoma development, including MYCN. NEN is currently used as an antiparasitic worm treatment and is safe to use in children but has poor pharmacokinetic properties. However, derivatives of NEN and structurally distinct uncouplers that have improved pharmacokinetic properties are in development. Results of this study ignite the idea that mitochondrial uncouplers could be used as differentiating agents and expand the pharmacotherapy toolkit to treat cancer, including neuroblastoma. See related article by Jiang et al., p. 181
Interferon Alfa-2b Adjuvant Therapy of High-Risk Resected Cutaneous Melanoma: The Eastern Cooperative Oncology Group Trial EST 1684
Authors: J M Kirkwood, M H Strawderman, M S Ernstoff, T J Smith, E C Borden, R H Blum
Journal: Journal of Clinical Oncology (2023)

Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma.
JAMA Dermatology
Journal: JAMA Dermatology (2023)

Mission Statement JAMA Dermatology's mission is to elevate the art and science of health and diseases of skin, hair, nails, and mucous membranes, and their treatment, to enable dermatologists to deliver evidence-based, high-value medical and surgical dermatologic care.The journal publishes a broad range of innovative studies and trials that shift research and clinical practice paradigms, expand the understanding of the burden of dermatologic diseases and key outcomes, improve the practice of dermatology, and ensure equitable care to all patients.The journal also features research and opinion examining ethical, moral, socioeconomic, educational, and political issues relevant to dermatologists to enable ongoing improvement to the workforce, scope of practice, and the training of future dermatologists.JAMA Dermatology aims to be a leader in developing initiatives to improve diversity, equity, and inclusion within the specialty and within dermatology medical publishing.
Nanomedicine based strategies for oligonucleotide traversion across the blood–brain barrier
Authors: Etikala Amulya, Anupama Sikder, Ganesh Vambhurkar, Saurabh Shah, Dharmendra Kumar Khatri, Rajeev Singh Raghuvanshi, Shashi Bala Singh, Saurabh Srivastava
Journal: Journal of Controlled Release (2023)
Tasquinimod suppresses tumor cell growth and bone resorption by targeting immunosuppressive myeloid cells and inhibiting c-MYC expression in multiple myeloma
Authors: Rong Fan, Hatice Satilmis, Niels Vandewalle, Emma Verheye, Philip Vlummens, Anke Maes, Catharina Muylaert, Elke De Bruyne, Eline Menu, Holly Evans, Andrew Chantry, Nathan De Beule, Dirk Hose, Marie Törngren, Helena Eriksson, Karin Vanderkerken, Ken Maes, Karine Breckpot, Kim De Veirman
Journal: Journal for ImmunoTherapy of Cancer (2023)

Immunotherapy emerged as a promising treatment option for multiple myeloma (MM) patients. However, therapeutic efficacy can be hampered by the presence of an immunosuppressive bone marrow microenvironment including myeloid cells. S100A9 was previously identified as a key regulator of myeloid cell accumulation and suppressive activity. Tasquinimod, a small molecule inhibitor of S100A9, is currently in a phase Ib/IIa clinical trial in MM patients (NCT04405167). We aimed to gain more insights into its mechanisms of action both on the myeloma cells and the immune microenvironment. We analyzed the effects of tasquinimod on MM cell viability, cell proliferation and downstream signaling pathways in vitro using RNA sequencing, real-time PCR, western blot analysis and multiparameter flow cytometry. Myeloid cells and T cells were cocultured at different ratios to assess tasquinimod-mediated immunomodulatory effects. The in vivo impact on immune cells (myeloid cell subsets, macrophages, dendritic cells), tumor load, survival and bone disease were elucidated using immunocompetent 5TMM models. Tasquinimod treatment significantly decreased myeloma cell proliferation and colony formation in vitro, associated with an inhibition of c-MYC and increased p27 expression. Tasquinimod-mediated targeting of the myeloid cell population resulted in increased T cell proliferation and functionality in vitro. Notably, short-term tasquinimod therapy of 5TMM mice significantly increased the total CD11b+ cells and shifted this population toward a more immunostimulatory state, which resulted in less myeloid-mediated immunosuppression and increased T cell activation ex vivo. Tasquinimod significantly reduced the tumor load and increased the trabecular bone volume, which resulted in prolonged overall survival of MM-bearing mice in vivo. Our study provides novel insights in the dual therapeutic effects of the immunomodulator tasquinimod and fosters its evaluation in combination therapy trials for MM patients.
Correction: Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma
Authors: Haowen Jiang, Rachel L. Greathouse, Sarah Jane Tiche, Man Zhao, Bo He, Yang Li, Albert M. Li, Balint Forgo, Michaela Yip, Allison Li, Moriah Shih, Selene Banuelos, Meng-Ning Zhou, Joshua J. Gruber, Erinn B. Rankin, Zhen Hu, Hiroyuki Shimada, Bill Chiu, Jiangbin Ye
Journal: Cancer Research (2023)

In the original version of this article (1), as it was published online on November 1, 2022, two of the datasets used for the analyses reported in Fig. 6A–D and Supplementary Table S3 (498-RPM-seqcnb1 and SEQC-498-custom-ag44kcwolf) were redundant. The authors have now removed 498-RPM-seqcnb1 and reperformed the analyses for prognostic gene sets of overall survival only, as opposed to the original version, which included both overall survival and event-free survival. These changes have been incorporated into the text, Fig. 6A–D, and Supplementary Table S3. The HTML and PDF versions of this article were corrected on January 3, 2023, ahead of print.